18 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE When heat was added to the equation changes occurred in the mean plasma concentration of the drug. In comparator trials the plasma concentrations reached were at least double after thirty minutes in the thermal group and this was maintained until sixty minutes. Prior to thirty minutes there was a time dependent improvement presumably because the applied heat caused a gradual increase in permeability of the urothelium. It has been noted that when a tumour is present at the time of chemo thermotherapy the plasma levels rise even higher presumably because of the increased vascularity of tumours. Fortunately, multiple tumours do not seem to result in a toxic dose. Furthermore, within the tumour tissue itself there is an up to ten-fold increase in drug concentration due to parameters of tumour tissue described earlier in the article. Mitomycin is metabolised in the target cells to three forms that are directly cytotoxic. The drug metabolism increases proportionally by fty percent for each 1°C rise in temperature thereby enhancing cancer cell destruction. You may ask does the heat not damage the drug and the answer seems to be no. There was almost no difference in the concentration levels of drug in the urine after treatment comparing thermal to non-thermal therapy controls. HIVEC Devices Hyperthermia can be delivered as a local, regional or as a whole-body therapy. With bladder cancer I will be considering local therapy only in its intravesical format. The bladder readily lends itself to this form of treatment as it is readily accessible from the outside and valves at the ureteric junctions and at the bladder neck mean the treatment can be conned solely to the bladder. There are machines that can deliver regional bladder hyperthermia. This hardware is extremely expensive and is unlikely to be purchased by a urologist. This hardware heats the bladder from the outside and can heat the entire bladder wall and the peri-vesical tissue. Work is being conducted to look at treating muscle invasive bladder tumours with this treatment modality. At last, I will now introduce the technologies developed for local chemohyperthermia of NIMBC. The story of chemohyperthermia starts back in 1972 when Thiotepa was used in conjunction with thermotherapy up to 44°C for low stage bladder tumours. The initial trials were not very successful with many side effects. In the 1980’s an existing microwave technology was combined with Mitomycin to develop the rst intravesical chemothermotherapy. Synergo The Synergo system was developed to improve chemo hyperthermia in the bladder by placing the heating source inside the bladder so no longer did energy have to travel from the outside to reach the bladder. This concept was akin to brachytherapy of the prostate instead of external beam radiation, a technique well known to urologists. A small diameter intraluminal microwave antenna was developed that was embedded in a multilumen catheter. The source of the microwave radiation was thus signicantly simplied bringing the cost of the treatment down. The microwave antenna not only heated the uid in the bladder lumen but also the bladder wall through radiation. By circulating the uid and cooling it the designers could achieve higher energy levels in the antenna. The greater energy meant improved penetration of heat through the bladder uid and into the bladder wall. The system has had several iterative improvements with time. However due to issues already mentioned it remained a tool of thermotherapists mainly. The
RkJQdWJsaXNoZXIy NTIyOTQ=